Is DUSP6 p.Val73Met (c.217G>A) pathogenic?

DUSP6 p.Val73Met (c.217G>A) is classified Uncertain significance in DUSP6 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-04). AlphaMissense: likely benign (0.1537); Very rare (popmax 0.00446%, eas).

How common is DUSP6 p.Val73Met (c.217G>A) in the general population?

DUSP6 p.Val73Met (c.217G>A) is very rare (popmax 0.00446%, eas) (gnomAD).

What do computational predictors say about DUSP6 p.Val73Met (c.217G>A)?

AlphaMissense predicts likely benign (score 0.1537) — an in-silico prediction, not a clinical call.

DUSP6 p.Val73Met

c.217G>A · VCV3676877

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1537 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1537	likely benign
REVEL	0.088	moderately benign-leaning
SaProt	LLR -9.24	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.6	GERP -0.64, phastCons 0.09
Regional constraint	o/e 1.00	unconstrained · MANE · 1,392 bp · p 0.98 · regional, not allelic
Overall
CADD	21.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00446% East Asian · 2/44,828 alleles

Filtering AF 0.00074% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000277%

Overall 0.000186% 3/1,611,364 alleles · very rare exomes 3/1,459,004 · genomes 0/152,360 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00446%	22,414
Admixed American	0.00167%	59,848

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: DUSP6
Protein: p.Val73Met
Coding: c.217G>A
MANE Select: NM_001946
Type: single nucleotide variant
Location: chr12:89351823 (GRCh38)
Gene constraint: LOEUF 0.45 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 76.13 · 2 PDB
Residue 73: the rhodanese domain; a turn

Full DUSP6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DUSP6 p.Ala141Asp Uncertain significance ★★ ⚠ same type
DUSP6 p.Ala57Thr Uncertain significance ★★ ⚠ same type
DUSP6 p.Asp93Glu Uncertain significance ★★ ⚠ same type
DUSP6 p.Glu32Lys Uncertain significance ★★ ⚠ same type
DUSP6 p.Gly30Cys Uncertain significance ★★ ⚠ same type
DUSP6 p.Phe77Ile Uncertain significance ★★ ⚠ same type
DUSP6 c.400+231T>C Benign ★★ same type
DUSP6 c.401-113T>A Benign ★★ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/dusp6-p-val73met (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown